The Indian Network of Drug-Induced Liver Injury: Etiology, Clinical Features, Outcome and Prognostic Markers in 1288 Patients.

BACKGROUND: Etiology of and outcomes following idiosyncratic drug-induced liver injury (DILI) vary geographically. We conducted a prospective study of DILI in India, from 2013 to 2018 and summarize the causes, clinical features, outcomes and predictors of mortality. METHODS: We enrolled patients with DILI using international DILI expert working group criteria and Roussel Uclaf causality assessment method. Follow-up was up to 3 months from onset of DILI or until death. Multivariate logistics regression was carried out to determine predictors of non-survival. RESULTS: Among 1288 patients with idiosyncratic DILI, 51.4% were male, 68% developed jaundice, 68% required hospitalization and 8.2% had co-existing HIV infection. Concomitant features of skin reaction, ascites, and encephalopathy (HE) were seen in 19.5%, 16.4%, and 10% respectively. 32.4% had severe disease. Mean MELD score at presentation was 18.8 ± 8.8. Overall mortality was 12.3%; 65% in those with HE, 17.6% in patients who fulfilled Hy's law, and 16.6% in those that developed jaundice. Combination anti-TB drugs (ATD) 46.4%, complementary and alternative medicines (CAM) 13.9%, anti-epileptic drugs (AED) 8.1%, non-ATD antimicrobials 6.5%, anti-metabolites 3.8%, anti-retroviral drugs (ART)3.5%, NSAID2.6%, hormones 2.5%, and statins 1.4% were the top 9 causes. Univariate analysis identified, ascites, HE, serum albumin, bilirubin, creatinine, INR, MELD score (p < 0.001), transaminases (p < 0.04), and anti-TB drugs (p = 0.02) as predictors of non-survival. Only serum creatinine (p = 0.017), INR (p < 0.001), HE (p < 0.001), and ascites (p = 0.008), were significantly associated with mortality on multivariate analysis. ROC yielded a C-statistic of 0.811 for MELD and 0.892 for combination of serum creatinine, INR, ascites and HE. More than 50 different agents were associated with DILI. Mortality varied by drug class: 15% with ATD, 13.6% with CAM, 15.5% with AED, 5.8% with antibiotics. CONCLUSION: In India, ATD, CAM, AED, anti-metabolites and ART account for the majority of cases of DILI. The 3-month mortality was approximately 12%. Hy's law, presence of jaundice or MELD were predictors of mortality.

Trends in oral anticoagulant use in Qatar: a 5-year experience.

In Qatar, dabigatran was introduced in 2011 followed by rivaroxaban in 2014. In this study, we aim to explore the trends in oral anticoagulant use in Qatar over the past 5 years and to what extent did DOACs replace warfarin. We also explored the extent of switching between different anticoagulants (from warfarin to DOACs and vice versa). We collected all anticoagulant prescriptions dispensed as in- or out-patient from 2011 to 2015 in all Hamad Medical Corporation (HMC) hospitals. Overall number of patients using warfarin, dabigatran and rivaroxaban over the last 5 years collectively was calculated. Per each calendar year, we calculated the number of all 3 OAC used (warfarin, dabigatran and rivaroxaban), frequency of use of each one of the OAC prescribed and compared the change in proportion of DOACs to warfarin prescriptions over the years. Overall, 6961 patients were using OAC over the past 5 years among which 5849 (84%) used warfarin, 496 (7.1%) used dabigatran and 616 (8.8%) used rivaroxaban. Oral anticoagulants use increased gradually from 2091 in 2011 to 3688 in 2015. Number of patients receiving DOACs increased significantly compared to warfarin [11 (0.5%) in 2011 vs. 849 (23%) in 2015 (p < 0.0001)]. Since its introduction in 2014, number of rivaroxaban users increased significantly compared to dabigatran [212 (40.9%) in 2014 vs. 544 (64.1%) in 2015]. DOACs have been gradually replacing warfarin in Qatar and the trend of their use is similar to that reported in other countries. Warfarin remains the most commonly used oral anticoagulant.

Use of complementary and alternative medicines during the third trimester.

OBJECTIVE: To estimate the prevalence, indications, and associated factors for complementary and alternative medicine use during the last trimester of pregnancy. METHODS: A questionnaire survey was conducted of women with a live birth (N=700) admitted to the postnatal unit at the Royal Aberdeen Maternity Hospital, northeast Scotland. Outcome measures included: complementary and alternative medicine used; vitamins and minerals used; reasons for complementary and alternative medicine use; independent associated factors for use; views; and experiences. Descriptive and inferential statistical analysis was performed. RESULTS: The response rate was 79.6% of eligible women. Two thirds of respondents (61.4%) reported using complementary and alternative medicine, excluding vitamins and minerals, during the third trimester. Respondents reported using a total of 30 different complementary and alternative medicine modalities, of which oral herbal products were the most common (38% of respondents, 40 different products). The independent associated factors for complementary and alternative medicine use identified were: complementary and alternative medicine use before pregnancy (odds ratio [OR] 4.36, 95% confidence interval [CI] 2.39-7.95, P<.001); a university education (OR 2.41, 95% CI 1.46-4.0, P=.001), and complementary and alternative medicine use by family or friends (OR 2.36, 95% CI 1.61-3.47, P<.001). There was no association with health care professional recommendations. Users were significantly more likely than nonusers to agree that complementary and alternative medicines were safer than prescribed medicines (P=.006), less likely to be associated with side effects (P≤.001), and could interfere with conventional medicines (P≤.001). CONCLUSION: Despite the majority of respondents, and notably users, being uncertain about their safety and effectiveness, complementary and alternative medicine modalities and complementary and alternative medicine products are widely used during the third trimester of pregnancy in this study population. Although prior use was the most significant independent associated factor, the role of family and friends, rather than health professionals, in the decision to use complementary and alternative medicine may be of concern. LEVEL OF EVIDENCE: III.

Complementary and alternative medicine use during early pregnancy.

OBJECTIVE: To determine the prevalence and explore predictors of Complementary and Alternative Medicine (CAM) use during early pregnancy. STUDY DESIGN: A questionnaire survey of pregnant women (500) attending for mid trimester scan at the maternity services in Grampian, North-East Scotland. Outcome measures included; CAM used; vitamins and minerals used; independent predictors of use; views and experiences. Descriptive and inferential statistical analysis. RESULTS: The response rate was 66%. Two thirds of respondents (63%) reported using CAM, excluding vitamins and minerals, during early pregnancy. Respondents reported using a total of 28 different CAM modalities, of which oral herbal products were the most common (37% of respondents, 25 different products). The independent predictors of CAM use identified were: use by family and friends (OR 4.1, 95% CI 2.3-7.3, p<0.001); ethnicity (non-white British) (OR 3.4, 95% CI 1.8-6.8, p<0.001); and use prior to pregnancy (OR 2.4, 95% CI 1.2-4.8, p=0.014). In comparison to prescribed medicines, most users were uncertain if CAM were safer (63%), more effective (66%), free from possible adverse effects (46%) or drug-CAM interactions (50%). CONCLUSIONS: Despite the majority of respondents being uncertain about their safety and effectiveness, CAM modalities and CAM products are widely used during the early stages of pregnancy in this study population. The role of family and friends rather than health professionals in the decision to use CAM may be of concern and requires further investigation.

Acute coronary syndrome and khat herbal amphetamine use: an observational report.

BACKGROUND: The khat plant is a stimulant similar to amphetamine and is thought to induce coronary artery spasm. Khat is widely chewed by individuals originating from the Horn of Africa and the Arabian Peninsula. The aim of this study was to evaluate the clinical characteristics and outcome of khat chewers presenting with acute coronary syndrome. METHODS AND RESULTS: From October 1, 2008, through June, 30, 2009, 7399 consecutive patients with acute coronary syndrome were enrolled in the Second Gulf Registry of Acute Coronary Events (Gulf RACE-2). Nineteen percent of patients were khat chewers; 81% were not. Khat chewers were older, more often male, and less likely to have cardiovascular risk factors. Khat chewers were less likely to have a history of coronary artery disease and more likely to present late and to have higher heart rate and advanced Killip class on admission. Khat chewers were more likely to present with ST-segment-elevation myocardial infarction. Overall, khat chewers had higher risk of death, recurrent myocardial ischemia, cardiogenic shock, ventricular arrhythmia, and stroke compared with non-khat chewers. After adjustment for baseline variability, khat chewing was found to be an independent risk factor of death and for recurrent ischemia, heart failure, and stroke. CONCLUSIONS: Our data confirm earlier observations of worse in-hospital outcome among acute coronary syndrome patients who chew khat. This worse outcome persists up to 1 year from the index event. This observational report underscores the importance of improving education concerning the cardiovascular risks of khat chewing.

Factors affecting the development of hypothalamus and pituitary lesions in fatal closed head injury: a prospective study.

OBJECTIVES: To determine the factors affecting the development of pituitary and hypothalamic lesions after fatal closed head injury. MATERIALS: Thirty-four patients with severe closed head injury succumbing to the effects of brain trauma before or during admission, whether managed conservatively or surgically, formed the study group. Clinical parameters, injury to death interval, radiologic data, and management details were taken into consideration. Autopsy was performed within 48 hours of death; hypothalamus and pituitary were carefully removed and evaluated for the presence of lesions on hematoxylin and eosin and immunohistochemical staining. RESULTS: Patients were categorized into early death group (n = 11, those succumbing before/on admission) and late death group (n = 23, those succumbing after admission). Histopathologic evaluation of pituitary revealed capsular hemorrhages in 50%, posterior pituitary hemorrhage in 25%, anterior pituitary infarct in 21.8%, and anterior pituitary hemorrhage in 6.2% patients. Hypothalamic hemorrhage was observed in 65.2% patients and infarcts in 17.3%. Lesions in hypothalamus and pituitary were significantly related to the presence of ventricular compression on computed tomography scan and survival of >24 hours after injury (p < 0.05). Capsular hemorrhage, anterior pituitary hemorrhage, and posterior pituitary hemorrhage were present in 40%, 10%, and 30% of the patients in the early death group when compared with 54.5%, 4.5%, and 22.7% of the patients in the late death group. Anterior pituitary infarcts were present in 10% of the patients with early deaths and 27.3% patients in the late death group. Hypothalamic hemorrhages were present in 44.4% of patients in early death and 78.6% in late death groups. Hypothalamic infarcts (40%) were present in the late death group only. Two patients (25%) in the early death group and 11 (84.6%) in the late death group had lesions in pituitary as well as hypothalamus (p < 0.05). CONCLUSIONS: Presence of ventricular compression on computed tomography scan and survival >24 hours after severe head injury has a significant correlation with the development of hypothalamic and pituitary lesions. Secondary insults account for a proportion of pituitary and hypothalamic lesions after trauma, which may be amenable to prevention by early intervention to treat raised intracranial pressure (ICP)/herniation.

Vitamin D and bone mineral density status of healthy schoolchildren in northern India.

BACKGROUND: Current data on the prevalence of vitamin D deficiency in India are scarce. OBJECTIVE: We assessed the calcium-vitamin D-parathyroid hormone axis in apparently healthy children from 2 different socioeconomic backgrounds in New Delhi, India. DESIGN: Clinical evaluation for evidence of vitamin D deficiency was carried out in 5137 apparently healthy schoolchildren, aged 10-18 y, attending lower (LSES) and upper (USES) socioeconomic status schools. Serum calcium, inorganic phosphorus, alkaline phosphatase, 25-hydroxyvitamin D [25(OH)D], and immunoreactive parathyroid hormone were measured in 760 children randomly selected from the larger cohort. Bone mineral density of the forearm and the calcaneum was measured in 555 children by using peripheral dual-energy X-ray absorptiometry. RESULTS: Clinical evidence of vitamin D deficiency was noted in 10.8% of the children. Children in the LSES group had a significantly (P < 0.01) lower 25(OH)D concentration (10.4 +/- 0.4 ng/mL) than did those in the USES group (13.7 +/- 0.4 ng/mL). Concentrations of 25(OH)D <9 ng/mL were seen in 35.7% of the children (42.3% in LSES; 27% in USES; P < 0.01). Boys had significantly (P = 0.004) higher 25(OH)D concentrations than did girls. There was a significant negative correlation between the mean serum immunoreactive parathyroid hormone and 25(OH) D concentrations (r = -0.202, P < 0.001). Mean forearm bone mineral density was significantly (P < 0.01) higher in the USES group than in the LSES group. CONCLUSION: A high prevalence of clinical and biochemical hypovitaminosis D exists in apparently healthy schoolchildren in northern India.

Prevalence of multiple micronutrient deficiencies amongst pregnant women in a rural area of Haryana.

UNLABELLED: Deficiencies of micronutrients (zinc, iron, folic acid and iodine) during pregnancy are known causes of Low Birth Weight (LBW). Studies have documented status of one or two micronutrients amongst pregnant women (PW). However, no attempt has been made to concurrently assess the prevalence of multiple micronutrient deficiencies and the factors associated with them amongst PW. OBJECTIVE: The present study was undertaken to assess the prevalence of multiple micronutrient deficiencies amongst PW in a rural area. METHODS: A community based cross sectional survey was conducted in six villages of a rural area of district Faridabad in Haryana state, India during November 2000 and October 2001. All PW aged 18 years or more, with pregnancy duration of more than 28 weeks were enrolled. Data were collected on socio-economic status and other demographic parameters. Serum zinc, copper and magnesium levels were estimated by utilizing the Atomic absorption spectrophotometry (AAS); serum ferritin and folate was estimated by Enzyme Linked Immuno Sorbent Assay (ELISA) method and the Radio-Immuno Assay (RIA) method, respectively and serum thyroid stimulating hormone (TSH) level was estimated by the Abbot AxSYM System. Serum zinc, copper, magnesium, ferritin, and folate levels less than 70.0 microg/dl, 80.0 microg/dl, 1.80 mg/dl, 15 ng/ml, and 3 ng/ml, respectively were considered as indicative of deficiency for respective micronutrients. The TSH levels of 4.670 and more indicated iodine deficiency status. Dietary intake of micronutrients was assessed utilizing 1-day 24-hour dietary recall methodology. Food consumption pattern was assessed utilizing the food frequency questionnaire methodology. RESULTS: Nearly 73.5, 2.7, 43.6, 73.4, 26.3, and 6.4 percent PW were deficient in zinc, copper, magnesium, iron, folic acid and iodine, respectively. The highest concurrent prevalence of two, three, four and five micronutrient deficiency was of zinc and iron (54.9%); zinc, magnesium and iron (25.6%); zinc, magnesium, iron and folic acid (9.3%) and zinc, magnesium, iron, folic acid and iodine (0.8%), respectively. No pregnant woman was found to have concomitant deficiencies of all the six micronutrients. Dietary intake data revealed an inadequate nutrient intake. Over 19% PW were consuming less than 50% of the recommended calories. Similarly, 99, 86.2, 75.4, 23.6, 3.9 percent of the PW were consuming less than 50% of the recommended folic acid, zinc, iron, copper, and magnesium. The consumption of food groups rich in micronutrients (pulses, vegetables, fruits, nuts and oil seeds, animal foods) was infrequent. Univariate and Multivariate logistic regression analysis revealed that low dietary intake of nutrients, low frequency of consumption of food groups rich in micronutrients and increased reproductive cycles with short interpregnancy intervals were important factors leading to micronutrient deficiencies. CONCLUSION: There was a high prevalence of micronutrient deficiencies amongst the PW of the area, possibly due to the poor dietary intake of food and low frequency of consumption of food groups rich in micronutrients. The concurrent prevalence of two, three, four and five micronutrient deficiencies were common.